Monoclonal antibodies specific to VEGF receptors and uses thereof

Abstract

Monoclonal antibodies that specifically bind to an extracellular domain of a VEGF receptor and neutralize activation of the receptor are provided. In vitro and in vivo methods of using these antibodies are also provided.

What is claimed is: 
     
       1. A process for preparing a polypeptide that comprises an amino acid sequence that specifically binds to an extracellular domain of a VEGF receptor and neutralizes activation of the receptor, the process comprising: culturing cells that express a nucleic acid molecule comprising a nucleic acid sequence that encodes an amino acid sequence wherein the amino acid sequence consists of the variable region of a monoclonal antibody that specifically binds to an extracellular domain of a VEGF receptor and neutralizes activation of the receptor; and   isolating the polypeptide from the cultured cells.   
     
     
       2. A process for preparing a polypeptide that comprises an amino acid sequence that specifically binds to an extracellular domain of a VEGF receptor and neutralizes activation of the receptor, the process comprising: culturing cells that express a nucleic acid molecule comprising a nucleic acid sequence that encodes an amino acid sequence wherein the amino acid sequence consists of the hypervariable region of a monoclonal antibody that specifically binds to an extracellular domain of a VEGF receptor and neutralizes activation of the receptor; and   isolating the polypeptide from the cultured cells.   
     
     
       3. A process for preparing chimerized monoclonal antibodies that specifically bind to an extracellular domain of a VEGF receptor and neutralize activation of the receptor, the process comprising: culturing cells that express a nucleic acid molecule comprising a nucleic acid sequence that encodes an amino acid sequence wherein the amino acid sequence consists of: (i) a variable region of a monoclonal antibody of a mammal other than a human wherein the variable region specifically binds to an extracellular domain of a VEGF receptor and neutralizes activation of the receptor, and   (ii) a constant region of a human antibody; and     isolating the chimerized monoclonal antibodies from the cultured cells.   
     
     
       4. A process for preparing humanized monoclonal antibodies that specifically bind to an extracellular domain of a VEGF receptor and neutralize activation of the receptor, the process comprising: culturing cells that express a nucleic acid molecule comprising a nucleic acid sequence that encodes an amino acid sequence wherein the amino acid sequence consists of: (i) a hypervariable region of a monoclonal antibody of a mammal other than a human wherein the hypervariable region specifically binds to an extracellular domain of a VEGF receptor and neutralizes activation of the receptor,   (ii) a constant region of a human antibody, and   (iii) a variable region, other than the hypervariable region, substantially from a human antibody; and     isolating the humanized monoclonal antibodies from the cultured cells.   
     
     
       5. A process for preparing a polypeptide that comprises an amino acid sequence that specifically binds to an extracellular domain of a VEGF receptor and inhibits tumor growth in a mammal, the process comprising: culturing cells that express a nucleic acid molecule comprising a nucleic acid sequence that encodes an amino acid sequence wherein the amino acid sequence consists of the variable region of a monoclonal antibody that specifically binds to an extracellular domain of a VEGF receptor and inhibits tumor growth in the mammal; and   isolating the polypeptide from the cultured cells.   
     
     
       6. A process for preparing a polypeptide that comprises an amino acid sequence that specifically binds to an extracellular domain of a VEGF receptor and inhibits tumor growth in a mammal, the process comprising: culturing cells that express a nucleic acid molecule comprising a nucleic acid sequence that encodes an amino acid sequence wherein the amino acid sequence consists of the hypervariable region of a monoclonal antibody that specifically binds to an extracellular domain of a VEGF receptor and inhibits tumor growth in the mammal; and   isolating the polypeptide from the cultured cells.   
     
     
       7. A process for preparing chimerized monoclonal antibodies that specifically bind to an extracellular domain of a VEGF receptor and inhibit tumor growth in a recipient mammal, the process comprising: culturing cells that express a nucleic acid molecule comprising a nucleic acid sequence that encodes an amino acid sequence wherein the amino acid sequence consists of: (i) a variable region of a monoclonal antibody of a mammal other than a human wherein the variable region specifically binds to an extracellular domain of a VEGF receptor and inhibits tumor growth in the recipient mammal, and   (ii) a constant region of a human antibody; and     isolating the chimerized monoclonal antibodies from the cultured cells.   
     
     
       8. A process for preparing humanized monoclonal antibodies that specifically bind to an extracellular domain of a VEGF receptor and inhibit tumor growth in a recipient mammal, the process comprising: culturing cells that express a nucleic acid molecule comprising a nucleic acid sequence that encodes an amino acid sequence wherein the amino acid sequence consists of: (i) a hypervariable region of a monoclonal antibody of a mammal other than a human wherein the hypervariable region specifically binds to an extracellular domain of a VEGF receptor and inhibits tumor growth in the recipient mammal,   (ii) a constant region of a human antibody, and   (iii) a variable region, other than the hypervariable region, substantially from a human antibody; and     isolating the humanized monoclonal antibodies from the cultured cells.